Substance use in psychiatric crisis: relationship to violence.

BACKGROUND: Substance use and psychiatric illness, particularly psychotic disorders, contribute to violence in emergency healthcare settings. However, there is limited research regarding the relationship between specific substances, psychotic symptoms and violent behaviour in such settings. We investigated the interaction between recent cannabinoid and stimulant use, and acute psychotic symptoms, in relation to violent behaviour in a British emergency healthcare setting. METHODS: We used electronic medical records from detentions of 1089 individuals under Section 136 of the UK Mental Health Act (1983 amended 2007), an emergency police power used to detain people for 24-36 h for psychiatric assessment. The relationship between recent cannabinoids and/or stimulant use, psychotic symptoms, and violent behaviour, was estimated using logistic regression. FINDINGS: There was evidence of recent alcohol or drug use in 64.5% of detentions. Violent incidents occurred in 12.6% of detentions. Psychotic symptoms increased the odds of violence by 4.0 [95% confidence intervals (CI) 2.2-7.4; p < 0.0001]. Cannabinoid use combined with psychotic symptoms increased the odds of violence further [odds ratios (OR) 7.1, 95% CI 3.7-13.6; p < 0.0001]. Recent use of cannabinoids with stimulants but without psychotic symptoms was also associated with increased odds of violence (OR 3.3, 95% CI 1.4-7.9; p < 0.0001). INTERPRETATION: In the emergency setting, patients who have recently used cannabinoids and exhibit psychotic symptoms are at higher risk of violent behaviour. Those who have used both stimulants and cannabinoids without psychotic symptoms may also be at increased risk. De-escalation protocols in emergency healthcare settings should account explicitly for substance use.

Effects of risk for bipolar disorder on brain function: A twin and family study.

Bipolar disorder (BPD) is associated with altered regional brain function during the performance of cognitive tasks. The relative contribution of genetic and environmental risk factors for BPD to these changes has not yet been quantified. We sought to address this issue in a functional neuroimaging study of people who varied in their risk for BPD. Functional magnetic resonance imaging was used to study 124 subjects (29 twin and 9 sibling pairs with at least one member with BPD, and 24 healthy twin pairs) performing a working memory task. We assessed the influence of risk for BPD on regional brain function during the task in a two stage process. Firstly, we identified areas where there were group differences in activation. Secondly, we estimated the heritability and phenotypic correlation of activation and BPD using genetic modeling. BPD was associated with increased activation in the anterior cingulate, orbitofrontal, medial prefrontal, and left precentral cortices, and in the precuneus. Within these regions, activation in the orbitofrontal cortex rendered the most significant heritability estimate (h2=0.40), and was significantly correlated with BPD phenotype (rph=0.29). A moderate proportion of the genetic influences (rg=0.69) acting on both BPD and on the degree of orbitofrontal activation were shared. These findings suggest that genetic factors that confer vulnerability to BPD alter brain function in BPD.

D-fenfluramine-evoked serotonergic responses in olanzapine-treated schizophrenic patients.

Antagonist activity at the 5-HT(2) receptor may contribute to the therapeutic efficacy of atypical antipsychotics in schizophrenia. This neuroendocrine study examined the in vivo functional serotonergic (5-HT) activity of the atypical antipsychotic olanzapine. We examined central 5-HT(2) responses by measuring the serum prolactin (PRL) over 5 h in response to 30 mg of D-fenfluramine (DFEN) in two groups of male schizophrenic patients. Blunted PRL responses to DFEN indicate functional 5-HT(2) receptor antagonism. Seven patients treated with olanzapine at a mean (S.D.) dose of 13.1 (4.6) for a mean of 28 weeks were compared with a matched group of eight patients who had received no antipsychotic treatment for at least 2 weeks. Baseline PRL levels did not differ significantly in the two patient groups and were within the normal range. The olanzapine-treated patients showed a significantly lower maximal DFEN-evoked PRL response and a significantly lower group x time overall PRL release compared with the untreated patient group. We have previously demonstrated a similar degree of functional in vivo 5-HT(2) antagonism with the atypical antipsychotic clozapine. This study thus suggests that this activity may not contribute to the unique clinical efficacy of clozapine.

The nature of abnormal language processing in euthymic bipolar I disorder: evidence for a relationship between task demand and prefrontal function.

OBJECTIVES: Abnormal language processing is a consistent finding in bipolar disorder (BD). We used functional magnetic resonance imaging (fMRI) to investigate the core components of language processing as well as the impact of task demand in a group of bipolar subjects. METHODS: Twelve euthymic dextral male BD I participants receiving lithium monotherapy were matched with 12 controls. Groups were matched for age, years of education and estimated premorbid IQ. We employed a factorial design manipulating task demand (decision versus fluency) and task domain (phonetic versus semantic) to investigate differences in language processing between groups and across different task domains and requirements. Data were fitted to haemodynamic response models convolved to the experimental design. Group and task difference maps were generated. RESULTS: During the scanning session bipolar patients demonstrated significantly slower reaction times. However, groups demonstrated the same task accuracy except for one domain (phonetic decision). All participants activated regions known to be engaged by language tasks, but compared to controls the bipolar patients showed altered patterns of prefrontal activation which were related to the nature of the task, language processing, and increasing task demand. CONCLUSIONS: We have demonstrated abnormal prefrontal activation in bipolar patients across a range of language tasks with varying task demands.

The bipolar spectrum: diagnostic and pharmacologic considerations.

Bipolar disorder represents a clinically challenging, episodic, lifelong medical illness that is both disabling and dangerous to the patient and is associated with a high risk of suicide. The prognosis for bipolar patients is likely to worsen with delays in accurate diagnosis and treatment as time is allowed for more extensive complications and morbidity to accrue and for alcohol or other substance use comorbidity to complicate the course of the illness. Physicians face several challenges when diagnosing bipolar disorder, including overlapping symptomatology and comorbidity with other disorders, as well as the somewhat restrictive and categorical approach taken by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and the International Statistical Classification of Diseases, 10th Revision (ICD-10) diagnostic criteria. As a result, bipolar disorder is frequently unrecognized and misdiagnosed with considerable clinical and prognostic consequences for the patient. The accuracy of diagnosis of bipolar disorder could be improved through the introduction of a refined procedure for the identification and evaluation of a broader range of symptoms, and by careful attention to the presence of subthreshold symptomatology. A conceptual shift toward acceptance of a 'spectrum' model of bipolar disorder and the development of appropriate clinical diagnostic tools should assist physicians in differentiating bipolar disorder from other Axis I, Axis II, and personality disorders, as well as ensuring early diagnosis and therapeutic intervention.

A functional MRI study of working memory task in euthymic bipolar disorder: evidence for task-specific dysfunction.

OBJECTIVES: Even when euthymic bipolar disorder patients can have persistent deficits in working memory, but the neural basis of this deficit remains unclear. We undertook an functional magnetic resonance imaging investigation of euthymic bipolar disorder patients performing two working memory paradigms; the two-back and Sternberg tasks, selected to examine the central executive and the phonological loop respectively. We hypothesized that neuronal dysfunction would be specific to the network underlying the executive rather than the phonological loop component of working memory. METHODS: Twelve right-handed euthymic bipolar I males receiving lithium carbonate monotherapy were matched with 12 controls. The two-back task comprised a single working memory load contrasted with baseline vigilance condition. The Sternberg paradigm used a parametric design incorporating variable working memory load with fixed delay between presentation of an array of items to be remembered and a target item. Functional activation data were acquired during performance of the tasks and were analysed to produce brain activation maps representing significant group differences in activation (ANOVA). Load-response curves were derived from the Sternberg task data set. RESULTS: There were no significant between-group differences (t-test) in performance of the two-back task, or in 2 x 5 group by memory load ANOVA for the performance data from Sternberg task. In the two-back task, compared with controls bipolar disorder patients showed reductions in bilateral frontal, temporal and parietal activation, and increased activations with the left precentral, right medial frontal and left supramarginal gyri. No between-group differences were observed in the Sternberg task at any working memory load. CONCLUSIONS: Our findings support the notion that, in euthymic bipolar disorder, failure to engage fronto-executive function underpins the core neuropsychological deficits.